The initial screening of bioactive agents, e.g., drug candidates, has typically been implemented in vitro. Although in vitro tests are practical, they often result in inaccurate data. Drugs that require metabolic activation are among the most promising therapeutic agents, for example, for use as anticancer drugs or antibiotics. However, these drugs can fail in in vitro tests, as the in vitro test systems often do not include all of the necessary enzymes, antibodies, and other compounds required for metabolic activation. Such drugs could therefore be abandoned without further investigation, regardless of their potential efficacy in an intact organism, simply because the in vitro studies might not unerringly mimic in vivo conditions. Likewise, a drug that is highly effective in vitro might not be viable in an organism if, for example, it is degraded or rendered toxic within the cell before reaching its target.
Previous in vivo tests of drug candidates have involved subdermal, subrenal, or peritoneal surgical implantation of a target cell line into a host animal, followed by administration of the drug candidate. Such studies can be misleading, however, as it is often difficult to account for interactions between the implanted cells and the cells of the host. For a similar reason, current in vivo studies are generally limited to the implantation of only a single target cell line into each host. Indeed, since the host animal generally must be sacrificed in order to recollect the implanted cells for analysis, such studies are often precluded by cost considerations, especially in higher mammals.
Examples of healthy cells include pancreatic islet tissue used in artificial pancreas devices. In other examples, Aebischer has implanted dopamine secreting neural cells for the treatment of Parkinson's disease (Exper. Neurology, 126:1-8, 1994) and encapsulated bovine chromaffin cells in sheep subarachnoid for the treatment of pain (Cell Transplantation, 3:243, 1994).